Walking is an extremely important and common daily activity. Many locomotor impairments increase people's risk of falling. The total costs of all fall-related injuries may reach $43.8 billion by 2020. As many as 60% of patients with lower extremity amputation fall each year. Falls are especially problematic for young patients with traumatic amputation, who fall slightly more than older patients. Most people fall while they are walking. Also, very limited scientific evidence exists to guide design of interventions to improve walking function in patients with amputation. Thus, there is a clear need to better understand how patients with lower limb amputation respond to ecologically relevant perturbations, to identify the biomechanical and neuromuscular strategies these patients use to recover balance after being perturbed, and to develop effective evidence based treatment strategies to help these patients improve their walking stability. Our lab has developed novel engineering approaches to measure walking stability that directly quantify how humans respond to small perturbations. The primary goal of this study is to develop interventions to help prevent falls. This requires intervening before the fall itself occurs. While falls themselves are very elusive events, significant stumbles are very common. In the elderly, stumbling or tripping causes more than half of all falls. Therefore, stumbling is one of the primary precursors to falling. Stumbles often lead to fear of falling, excessive caution, and decreased physical activity. Surprisingly, however, no study has quantified stumbling responses in patients with lower limb amputation. For this project, we will first determine how patients with trans-tibial amputation respond to small, continuous pseudo-random visual or mechanical perturbations, similar to those they might experience walking outdoors over uneven terrain or in crowded public places. We will also directly test the common clinical assumption that these patients rely more heavily on vision because of their loss of distal somatosensory feedback. Second, we will determine how patients with trans-tibial amputation respond to large discrete mechanical perturbations during walking, such as they might experience when tripping over a curb or stepping in a pothole. From these data, we will identify specific biomechanical and neuromuscular strategies amputees use to recover balance after they stumble. Finally, we will determine if targeted virtual reality based gait training is more successful than conventional therapy for improving walking stability in patients with trans-tibial amputation. A fully immersive virtual environment will allow us to apply highly controlled and ecologically relevant perturbations, which we anticipate will generalize more readily to real world walking. This study will apply novel experimental and rigorous analytical approaches to significantly improve our understanding of how patients with amputation respond to perturbations. We will translate this knowledge into clinical practice by developing rehabilitation interventions based on our scientific findings. Finally, this work will provide a scientific basis for developing better interventions to improve walking function in populations with other walking related impairments. PUBLIC HEALTH RELEVANCE: Falls and the injuries that result from falls are a significant health care problem for the thousands of patients who undergo lower limb amputation every year, as well as for millions of elderly and patients with other locomotor impairments. Determining how these patients use their available sensory and motor resources to regulate stability during walking and developing effective evidence based treatment strategies to improve their walking stability will significantly extend and improve the lives of these patients. The proposed work will apply novel state-of-the-art experimental and analytical approaches to directly address these critical issues.